Main Outcome Measures For depression: the Hamilton DepressionRating Scale and the Beck Depression Inventory; and for mentaland physical functioning: the SF-12 Mental and Physical CompositeScales and treatment satisfaction.

In many primary care settings, particularly in managed care,nurses have played an important role in improving care for chronicdiseases, including arthritis9 and hypertension.33 In a short-terminpatient psychiatric unit, nurse telephone follow-up helpedreduce readmissions.34 Also, peer support has been effectivelyused with patients with cancer, schizophrenia, and substanceabuse.35-40 We hypothesized that having nurses and peers assistin the treatment of depression is an efficient way to improveoutcomes.

We developed a model for treating depression in primary carethat includes physician education and telephone follow-up andsupport by trained primary care nurses ("telehealth care").In addition, we developed a model of peer support provided bysuccessfully treated, formerly depressed health plan members.We aimed to demonstrate high feasibility, easy implementation,and improved patient outcomes and satisfaction.

Patients were referred by physicians at the Hayward and SanFrancisco primary care clinics within Kaiser Permanente NorthernCalifornia. Wall charts were placed in examining rooms showingthe Diagnostic and Statistical Manual of Mental Disorders, FourthEdition,41 criteria for major depressive disorder; characteristicsof patients who should be referred directly to specialty care;and recommended starting doses for selective serotonin reuptakeinhibitor medications. Ninety primary care physicians and 10nurse practitioners received 2 hours of structured trainingand at least 1 hour of booster training on the detection andmanagement of depression.

STUDY POPULATION

Patients eligible for the study were diagnosed by a primarycare physician as having major depressive disorder or dysthymiaand given a prescription for a selective serotonin reuptakeinhibitor antidepressant. Study participants were prescribedeither fluoxetine hydrochloride or paroxetine, reflecting prescribingpractices in primary care at the time of the study. Potentialparticipants were excluded if they received a previous antidepressantdrug prescription within the past 6 months, had an inadequatecommand of the English language, reported current problems withsubstance abuse, showed current suicide risk, or reported thoughtsof violence.

TREATMENT ASSIGNMENT

Patients were recruited during an 18-month period. Those whowere eligible and consented were randomly assigned to 1 of 3conditions: (1) usual physician care (physician counseling andtreatment with a selective serotonin reuptake inhibitor medication),(2) usual physician care plus nurse telehealth care, or (3)usual physician care plus nurse telehealth care plus peer support.During the initial 9 months of recruitment, patients were randomizedonly to conditions 1 or 2, with a 40% probability of assignmentto condition 1. During the remaining 9 months of recruitment,patients were assigned to all 3 conditions, with 40% assignedto condition 1, 20% to condition 2, and 40% to condition 3.By design, then, the overall study population was allocated40% to condition 1, 40% to condition 2, and 20% to condition3; thus, 40% of patients were assigned to an intervention withouttelehealth care and 60% were assigned to an intervention thatincluded telehealth care. The allocation ratios were designedto change over time so that we could begin the study beforewe were prepared to deliver the peer intervention. Randomizationwas stratified by facility. Consent and other procedures ofthe study were approved by the institutional review board ofKaiser Permanente.

PROCEDURES

Almost all of the patients referred to the study were recruitedthrough an in-person interview with a research assistant immediatelyafter the clinic visit that led to the referral. The rest ofthe patients were recruited by telephone within 3 days of referral.During the interview each patient's eligibility was checked,the study was explained, informed consent was obtained, andbaseline data were collected. Baseline measures included theself-report version of the Hamilton Depression Rating Scale,42-44the Beck Depression Inventory,45 and the SF-12 Mental and PhysicalComposite Scales.46-48 The SF-12 scales measure perceived impairmentof functioning due to mental and physical disorders, respectively.Follow-up measures were the same with 2 exceptions. The HamiltonDepression Rating ScaleInterview49 was used rather thanthe self-report version. Previous investigators44, 49 founda high correlation between the self-report and interview versionsof the Hamilton scale. The second exception was the deletionof the SF-12 Physical Composite Scale. This measure was includedonly at baseline to control for global severity of physicalillness.

Our primary measure of symptomatic outcome was the HamiltonDepression Rating Scale. This instrument was expected to bethe most sensitive measure of symptomatic effects because ithas shown this superiority in previous studies.50-53

Trained Kaiser Permanente interviewers (all graduate studentsin psychology) assessed each patient by telephone 6 weeks and6 months after study entry. The Beck Depression Inventory wasmailed to participants in advance, and their answers were gatheredvia the telephone. All patients were sought for interview atboth follow-up times regardless of their current treatment status,residence location, or membership status in the Kaiser PermanenteHealth Plan.

Four interviewers were trained by the project clinical director(J.F.M.). Training consisted of mock interviews in which theywere taught how to rate the Hamilton Depression Rating Scale,followed by practice interviews in which their ratings werereviewed, critiqued, and discussed. Training on the other studyinstruments consisted of several mock interviews that were observedand critiqued. Interviewers were allowed to evaluate study patientsonly after they had successfully completed training. Duringthe study, 2 pairs of interviewers periodically audited eachother's Hamilton interviews and scored them independently. Interratercorrelations were 0.95 (n = 31) and 0.97 (n = 35).

The patient satisfaction with treatment scale consists of 11items rated on a 5-point scale from 5 ("very satisfied") to1 ("very dissatisfied"). A principal components factor analysiswith varimax rotation factor analysis of the satisfaction itemsfrom the 6-week interview produced 2 factors that accountedfor 100% of the shared variance among the items. Factor 1 reflectsthe degree of general satisfaction with the treatment servicesrespondents received and with the health maintenance organization,whereas factor 2 reflects satisfaction with the informationprovided about medications and medication side effects. Thescale and its factor structure are available from the authors.

Medication adherence data were gathered from computerized pharmacyrecords showing every prescription filled by study patientsat a Kaiser Permanente pharmacy. We measured total milligramsof selective serotonin reuptake inhibitors dispensed within6 weeks and 6 months of randomization. We excluded 15 patientsat 6 weeks and 20 at 6 months who had terminated their KaiserPermanente Health Plan membership or had filled antidepressantprescriptions in a nonKaiser Permanente pharmacy up tothe time of the analysis.

INTERVENTIONS

Usual Physician Care

Patients assigned to this condition continued to be seen asneeded by their primary care physician and, except for the 2experimental interventions, could be referred for other careas indicated. As previously described, most study physicianshad received at least 3 hours of training on the identificationand treatment of depression. They were asked to continue thesame pattern of follow-up visits with the patient regardlessof the study arm to which the patient was assigned. It was ourgoal to have usual physician care represent good care. We madeit explicit that we did not intend any reduced contact withthe treating physician to "offset" the cost of the supplementalinterventions.

Nurse Telehealth Care

Nurse telehealth care consisted of 1 to 2 telephone calls perweek during the first 2 weeks of enrollment, 1 call per weekduring weeks 3 to 8, and then 1 call every 2 weeks up to week16. The goal was to have 12 to 14 calls to each patient during16 weeks. Calls were limited to 10 minutes and were scheduledin advance. Extra calls were permitted in urgent circumstances,and the patient could leave telephone messages for the nurse.

In each telephone call the nurse inquired about questions thepatient might have had about the antidepressant medication,offered suggestions about how to deal with minor side effects,and emphasized the importance of taking the medication regularly.The nurse offered emotional support and helped patients identifyactivities that they were willing to try to be more active andto find pleasure. During each telephone call the nurse reviewedthe activities of the previous week. With the patient, she developeda plan for the next steps in doing these activities. Follow-upnurses were members of the patient's primary care clinic. Thiswas an advantage for patients because the nurse could also addressissues about other medical conditions and discuss the patient'soverall health as well as his or her mental health. By usingregular clinic nurses we therefore hoped to improve the overallcare of the patient, not just the care for depression. A logfor each telephone call included current medication and dosage,side effect problems, and a behavioral plan. The nurse gaveregular feedback on the progress of each patient to the patient'sprimary care physician.

Telehealth care nurses were chosen by a nursing supervisor ateach site based on the nurse's interest in the project and administrativestaffing considerations. Fifteen nurses completed a manualized6-hour training workshop developed and presented by the projectclinical director (J.F.M.). In treating study patients we useda single trained nurse at each site with an alternate to coverleave time. Nurses received ongoing weekly supervision fromthe clinical director, a clinical psychologist, mostly by telephonebut with 1 visit to a site each month.

Peer Support

Peer support was provided by health plan members who had experienceda successfully treated episode of major depression or dysthymiaand who volunteered to be trained as peer supporters. In eachcase the volunteer's mental health provider endorsed his orher participation in the program. Volunteers were recruitedthrough newspaper advertisements, notices posted in Kaiser Permanentewaiting rooms, and local television and radio news coverage.All volunteers were carefully screened by an experienced psychiatricsocial worker, who also trained the volunteers, matched themto study patients, and monitored their performance.

Training lasted approximately 20 hours and consisted of lectures,role play, and discussion. Peer supporters were supposed tomodel and share their successful coping skills, provide emotionalsupport, and encourage self-monitoring and a continued connectionto Kaiser Permanente depression care. They were also expectedto help patients develop and keep a hopeful outlook.

Peers were linked with study patients of similar age and sexwho had been assigned to the peer support condition. When possible,peers were also linked by similar life experience such as jobloss, divorce, or a similar medical problem. Peers were expectedto make a telephone or in-person contact with the patient on1 or more occasions, continuing to contact the person to expressan interest in how they were doing for at least 6 months aftertheir assigned person entered the study. Incentives such asmovie tickets were offered to encourage face-to-face contact.

STATISTICAL ANALYSIS

Dependent variables were total score on the Hamilton DepressionRating Scale, total score on the Beck Depression Inventory,2 satisfaction factor scores, and the SF-12 Mental FunctioningScale score. Consistent with previous research8, 18, 50-52 onthe treatment of depression in primary care, results for theHamilton Depression Rating Scale and the Beck Depression Inventorywere reported as means and as 50% improvement rates. The ratewas calculated by assigning a score of 1 if the patient showedan improvement of 50% or more from baseline and 0 if there wasless than a 50% improvement from baseline.

The analytic strategy was to focus sequentially on the 3 studyhypotheses. To test the first study hypothesis, that nurse telehealthcare leads to better outcomes than usual physician care, wecompared these 2 intervention groups on each outcome variablewhile controlling for the baseline level of that outcome. Whencomparing the means on quantitative variables, we carried outan analysis of covariance with usual physician care vs nursetelehealth care as the independent variable and the baselinevalue of the dependent variable as a covariate. We plotted residualsand found that variances were homogeneous over the range ofpredicted values. When analyzing the 50% improvement rates,we used logistic regression. Again, we used the baseline valueof the dependent variable as a covariate. The 2 satisfactionfactor scores were evaluated using the Wilcoxon rank sum test.We conducted all of these analyses separately at 6 weeks andat 6 months.

There is a potential threat to validity from the change in therandomization proportions made midway through patient recruitment.To check for possible bias, the analyses were re-run stratifiedby randomization method. We report any significant randomizationmethod by treatment group interactions.

The second hypothesis, regarding the effect of nurse telehealthcare on medication adherence, was tested using 3 interview questionscovering current antidepressant drug use. Computerized pharmacydata were used to compute mean milligrams dispensed from baselineto 6 weeks and from baseline to 6 months. Comparisons were madeusing 2 and t tests as appropriate at each time.

The third hypothesis, regarding the effects on outcomes of addingpeer support to nurse telehealth care, was tested by addingan additional contrast into the previous analyses. We comparedpatients who received nurse telehealth care plus peer supportwith those who received nurse telehealth care alone.

Four hundred eighty-six patients were referred to the study;116 were ineligible, 68 refused to give informed consent, and302 were enrolled. The main reasons for ineligibility (somepatients had several) included refusing the recruitment interview(n = 46), requiring referral to other treatment (n = 30), currentlyreceiving an antidepressant drug or psychotherapy (n = 21),refusing the prescribed selective serotonin reuptake inhibitor(n = 8), and not being literate in English (n = 8). There wasno difference between the 184 nonparticipants and the 302 participantsin age and sex, the only data available for nonparticipants.

Women comprised 69% of the sample. The average age was 55.4years (range, 19-90 years). Patients were white (63%), Hispanic(16%), African American (9%), Asian (7%), and of other racialand ethnic backgrounds (5%). The population was well educated:90% were high school graduates and 27% were college graduates.Household income was reported to be less than $25,000 by 34%of the sample and greater than $60,000 by 18%. More than halfof the participants lived with a spouse or partner, and 22%lived alone. Full- or part-time employment was reported by 53%of the sample, of whom 49% reported that they held managerialor professional or technical positions.

Using the unbalanced randomization described in the "TreatmentAssignment" subsection of the "Patients and Methods" section,123 patients (41%) were assigned to usual physician care, 117(39%) to nurse telehealth care, and 62 (21%) to nurse telehealthcare plus peer support. Table 1 shows that there were no significantdifferences between those assigned to nurse telehealth carevs usual physician care on any of the demographic variablesor in baseline values of dependent variables. Although peersupport vs no peer support comparisons within the telehealthcare group are not emphasized in this article, those subgroupswere also similar at baseline on all variables. The proportionof patients initially prescribed fluoxetine vs paroxetine wasalmost identical across all treatment groups.

Eight of 179 patients randomized to nurse telephone follow-upwere unable to be reached by trained primary care nurses. Thenurses made a mean (SD) of 10.1 (3.6) calls per patient to the171 patients who spoke to a nurse at least once during the 4months of intervention. These calls lasted a mean (SD) of 5.6(2.3) minutes. The estimated time for each telephone call, includingcallback attempts and documentation, was 20 minutes. We estimatethat 20 patients could be contacted in a full workday.

Peer Care

Of 62 patients randomized to peer support, 11 refused a peerassignment and 9 never had a peer contact for other reasons.Among the remaining 42 patients, 11 had 1 contact, 13 had 2contacts, 14 had 3 to 5 contacts, and 4 had 9 to 20 contacts.Most patients were only contacted by telephone, but 6 had atleast 1 face-to-face contact.

Our midstream change in the randomization allocation introducesa risk that differences between the first and second cohortmight bias the evaluation of treatment effectiveness. To checkwhether there was bias, we examined whether randomization cohortinteracted significantly with treatment assignment for any outcomevariable. Of the 7 outcome variables, only the SF-12 MentalFunctioning Scale showed an interaction. The interaction wassignificant at 6 weeks (P = .03) and a trend at 6 months (P= .10). In the early cohort there was little advantage for nursetelehealth care at 6 weeks but a large advantage at 6 months.In the late cohort there was a large advantage for telehealthcare at 6 weeks, but the 2 treatment groups converged by 6 months.The results shown in Table 2 are the average of these effects,which was significant at 6 weeks and a trend at 6 months, bothfavoring nurse telehealth care. Thus, the interaction with randomizationcohort does not change the SF-12 Mental Functioning Scale findings.

Effect of Nurse Telehealth Care on Medication Adherence

Contrary to our second hypothesis, we did not find that medicationadherence improved with nurse telehealth care. At 6 weeks, 73%of the usual care patients and 80% of those receiving nursetelehealth care reported taking an antidepressant medication(P = .17), whereas at 6 months 54% in usual care and 56% innurse telehealth care were taking an antidepressant medication(P = .74). For those still taking an antidepressant, there wereno significant differences in days missed in the past week ordays on which they took less than the prescribed dose. Antidepressantdispensing data from our pharmacy database show that treatmentgroups did not differ in mean milligrams dispensed during thefirst 6 weeks of enrollment (usual physician care = 957, nursetelehealth care plus peer support = 867, t286 = 1.13; P = .26)or from enrollment to 6 months (usual physician care = 2267,nurse telehealth care plus peer support = 2111, t281 = 0.73;P = .45). If anything, the trends suggest that patients receivingusual care used more medication. When we repeated these analysesin subgroups who were above or below a baseline Hamilton DepressionRating Scale score of 19.75, we also found no significant differences.

Added Value of Peer Support Beyond Nurse Telehealth Care

The same variables shown in Table 2 were used to compare outcomesat 6 weeks and 6 months between nurse telehealth care and thecombination of nurse telehealth care and peer support. Of the14 tests in Table 2, none showed significant additive effectsof peer support. There were other outcome variables gatheredthat we thought might reflect specific effects of peer support,and there were a few that showed effects at 6 months. Thesewill be presented elsewhere.

We sought an effective model for improving depression treatmentoutcomes that could be implemented easily within busy primarycare settings. Our model uses the nurses already in the primarycare setting, builds on the existing bond between primary careproviders and patients, and provides expert consultation andtreatment by mental health specialists when necessary. The modeluses medication, behavioral activation, education, brief counseling,emotional support, monitoring of suicide risk, and integrationof depression care with ongoing care for other chronic illnesses.

Our findings regarding nurse telehealth care have been receivedwith great interest by clinical leaders in the Kaiser PermanenteHealth Plan and in other health maintenance organizations. Animplementation kit is being distributed to other Kaiser Permanenteregions as part of a new depression disease management programdeveloped by Kaiser Permanente's Care Management Institute.

We expected that one reason nurse telehealth care would be superiorto usual patient care is that it would increase patients' adherenceto their prescribed medication. We did not find this. Althoughfurther work is needed to better understand the reasons forthe effect, the mechanism seems to be more psychosocial thanpharmacological.

Nurse telehealth care is significantly more effective than usualcare. But is the difference clinically important? The most recentmeta-analyses54-55 of antidepressant drug treatment estimateda response rate of 50% for antidepressant medications vs 32%for placebo in major depressive disorder. Similarly, antidepressanttreatment for dysthymia produced a 59% response vs 37% for placebo.Nurse telehealth care produces a 57% response rate vs 38% forusual care. The difference between nurse telehealth care andusual care is almost as large as that between drug and placebo.

Comparisons specific to primary care can be made using 2 studiesby Katon et al.8, 53 In one study (n = 217), usual care wascompared with collaborative care that involved increased physicianvisits during the first 4 to 6 weeks of treatment, including2 visits by the primary care physician and 2 or more by a psychiatrist.Eighty-nine percent of all patients in this study were treatedwith tricyclic antidepressant drugs. In the other study (n =153), usual care was compared with a structured depression treatmentprogram provided in four to six 30-minute sessions with doctoral-levelpsychologists that included behavioral treatment to increasethe use of adaptive coping strategies and counseling to improvemedication adherence. The percentage of patients who startedtaking tricyclic antidepressant drugs in this study was notreported but probably included a larger proportion who had beguntaking selective serotonin reuptake inhibitors. In both studies,patients were stratified by severity into those with major vsminor depression, and the enhanced intervention showed a clearadvantage for major depression. It showed a much smaller ornonsignificant advantage for minor depression. Although it isdifficult to compare the effects on depressive symptoms thatKaton et al8, 53 obtained with those of nurse telehealth carebecause different measures were used, the size of their effectson major depression seems similar to what we saw in our totalsample of patients with major depression or dysthymia.

Another difference was the intervention comparison. Althoughall 3 studies differed in the specific content of the interventions,both of the Katon et al8, 53 interventions involved considerableadditional patient contact by physicians or doctoral-level psychologists,whereas the intervention reported herein used less staff time,mostly of primary care nurses.

Peer support was operationally feasible in our setting in thesense that we could recruit, train, and match a sufficient numberof qualified peers. However, unlike nurse telehealth care, wedid not set specific expectations for the number and type ofcontacts between peers and patients. As a result, only halfof the patients randomized to peer support had more than 1 contactwith a peer and less than 10% had a face-to-face contact. Thiswas less than we had hoped for. Although we did not find thatpeer support improved our primary outcomes in the presence ofnurse telehealth care, we think it might be worthwhile to exploreits value when it is more clearly structured and is the onlyaugmentation to usual physician care.

This is only the first evidence of the effectiveness of nursetelehealth care, and the findings need to be replicated in othercircumstances to judge how confidently we can recommend broadadoption. If nurse telehealth care is broadly effective, itsmain advantage will be its ease of implementation in primarycare settings because it does not require major staffing changes.We also believe that nurse telehealth care can be improved withfurther research.

This research was supported in part by grants from the InnovationsProgram of Kaiser Permanente Northern California, Oakland, andthe Community Services Program of The Kaiser Permanente MedicalCare ProgramCalifornia Division, and by an unrestrictededucation grant from SmithKline Beecham Pharmaceuticals. Thisstudy is part of Kaiser Permanente's Depression Initiative,sponsored by the Garfield Memorial Fund.

We thank the following individuals for their contributions tothis study: Elvira Z. Mann, RN, and Ann Green, RN, of the KaiserPermanente (KP) Medical Centers at Hayward and San Francisco,Calif, respectively, for their provision of telehealth careto the intervention group; A. Gerson Schreiber, MD, and RaymondZablotny, MD, of the KP Medical Centers at Hayward and San Francisco,respectively, for developing and leading the physician and nursepractitioner training; Neil S. Handleman, MD, and Leslie M.Lopato, MD, of the KP Medical Centers at Hayward and San Francisco,respectively, for assisting with the physician and nurse practitionertraining; Viki Maxwell of the KP National Member TechnologyGroup for project coordination; Luz de la Riva of the KP Divisionof Research in Oakland, Calif, for successfully recruiting patientsinto the study; Chanda Rankin and Alexandra Chase, MA, of theKP Division of Research for successfully conducting follow-upinterviews with patients; David Cherry of the KP Division ofResearch for data management and editorial assistance; StewartProctor, PhD, of The Permanente Medical Group Inc. RegionalOperations Support Services at Oakland for coordination withthe Department of Psychiatry at Hayward; Robin A. Dea, MD, chairof the Chiefs of Psychiatry, KP Northern California, for cooperationand advice on clinical and implementation matters throughoutthe course of the study; Scott A. Bull, PharmD, of the KP Divisionof Research for assistance with analysis and interpretationof medication adherence data; Carol P. Somkin, PhD, of the KPDivision of Research for assistance in designing the peer supportintervention; A. Thomas McLellan, PhD, of the University ofPennsylvania, Philadelphia, for thoughtful comments on the studydesign; and Joe V. Selby, MD, of the KP Division of Researchfor insightful editorial comments.

A Taxonomy for Disease Management: A Scientific Statement From the American Heart Association Disease Management Taxonomy Writing Group
Krumholz et al.Circulation 2006;114:1432-1445.ABSTRACT
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